Cancer is caused by genetic aberrations, i.e., mutations. In mutant cells the normal balance between the factors that promote and restrain growth is disrupted, and as a result, these mutant cells proliferate continuously—the hallmark of tumor cells. Mutations can arise spontaneously or by external factors such as chemical mutagens, radiation, or viral integration, which inserts extra-genomic DNA that may or may not contain an oncogene. A cellular gene can be modified by point mutation, insertion and frame shift (including truncation), (functional) deletion (including silencing), or translocation, which sometimes can result in gene fusion. In this way, proto-oncogenes become oncogenes, which promote proliferation, and tumor suppressor genes become inactivated, also inducing tumor growth. Any combination of the above-mentioned changes in DNA can contribute to tumor formation. There are two ways by which mutations result in transformation: the expression level of the genes is changed, or their function is altered. The consequences of these changes may or may not be held in check by the immune system (immune surveillance).
Heretofore, there has been no demonstrated link between changes in ADAMTSL4 levels and kidney and/or colorectal cancer. Such a link could have a number of important diagnostic and therapeutic applications. It has now been discovered that (i) ADAMTSL4 levels change, e.g. decrease significantly in kidney cancer and colon tumor cells, and (ii) this change can be measured in blood-fluid and urine sample of patients.